| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From Neurologia Prima (Dr. Tiraboschi), Ospedali Riuniti, Bergamo, Italy; the Department of Neurosciences (Drs. Hansen, Sabbagh, Masliah, Thal, and Corey-Bloom, and M. Alford), University of California, San Diego, La Jolla; and Neurology Service (Drs. Sabbagh, Schoos, Thal, and Corey-Bloom), VA Medical Center, San Diego, CA.
Address correspondence and reprint requests to Dr. Jody Corey-Bloom, Neurology Service (9127), VA Medical Center, 3350 La Jolla Village Dr., San Diego, CA 92161; e-mail: jcoreybl{at}vapop.ucsd.edu
OBJECTIVE: To evaluate cholinergic activity in diseases with Lewy bodies (LB; LB variant of AD [LBV], diffuse LB disease [DLBD], and Parkinson’s disease [PD]) to determine if 1) AD changes are requisite to cholinergic dysfunction, 2) cholinergic activity declines to the same extent in neocortical and archicortical areas, and 3) cholinergic loss is influenced by APOE genotype.
BACKGROUND: Like AD, diseases with LB are associated with decreased choline acetyltransferase (ChAT) activity. Increased APOE 
4 allele frequency has been reported in LBV. Whether APOE genotype affects cholinergic function in LBV remains unclear.
METHODS: An autopsy series of 182 AD (National Institute on Aging and Consortium to Establish a Registry for Alzheimer’s Disease criteria), 49 LBV, 11 PD, 6 DLBD, and 16 normal control (NC) subjects. APOE genotype and ChAT activity (nmol/h/100 mg) in the midfrontal and hippocampal cortices were determined.
RESULTS: Mean midfrontal ChAT activity was markedly reduced in diseases with LB (LBV: 53.3 ± 39.0; PD: 54.8 ± 35.7; DLBD: 41.3 ± 24.8) compared to NC (255.4 ± 134.6; p < 0.001) and AD (122.6 ± 78.9; p < 0.05). Among diseases with LB, midfrontal ChAT activity was decreased to a similar extent in patients with (LBV) and without (DLBD and PD) AD pathology. Although mean ChAT activity for LBV was less than half that for AD in the midfrontal cortex, it was similar to that for AD in the hippocampus (LBV: 243.5 ± 189.7; AD: 322.8 ± 265.6; p > 0.05). However, hippocampal ChAT activity for both AD and LBV was lower than that for NC (666.5 ± 360.3; p < 0.001). The 4 allele dosage did not influence midfrontal ChAT activity in LBV.
CONCLUSIONS: Marked losses in midfrontal ChAT activity occur in diseases with LB, independent of coexistent AD changes. A greater midfrontal, as opposed to hippocampal, cholinergic deficit may differentiate LBV from AD. The lack of a relationship between 4 allele dosage and midfrontal ChAT activity suggests that other factors may play a role in its decline in LBV.
Key words: Cholinergic dysfunction—Lewy body disease—APOE—AD
This article has been cited by other articles:
|
|
 |
|
  P. Bentley, J. Driver, and R. J. Dolan Cholinesterase inhibition modulates visual and attentional brain responses in Alzheimer's disease and health Brain, February 1, 2008; 131(2): 409 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ballard, I. Ziabreva, R. Perry, J. P. Larsen, J. O'Brien, I. McKeith, E. Perry, and D. Aarsland Differences in neuropathologic characteristics across the Lewy body dementia spectrum Neurology, December 12, 2006; 67(11): 1931 - 1934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D J Burn, E N Rowan, L M Allan, S Molloy, J T O'Brien, and I G McKeith Motor subtype and cognitive decline in Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies J. Neurol. Neurosurg. Psychiatry, May 1, 2006; 77(5): 585 - 589. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Ellis Cholinesterase Inhibitors in the Treatment of Dementia J Am Osteopath Assoc, March 1, 2005; 105(3): 145 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. P. Mosimann, G. Mather, K. A. Wesnes, J. T. O'Brien, D. J. Burn, and I. G. McKeith Visual perception in Parkinson disease dementia and dementia with Lewy bodies Neurology, December 14, 2004; 63(11): 2091 - 2096. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Emre, D. Aarsland, A. Albanese, E. J. Byrne, G. Deuschl, P. P. De Deyn, F. Durif, J. Kulisevsky, T. van Laar, A. Lees, et al. Rivastigmine for Dementia Associated with Parkinson's Disease N. Engl. J. Med., December 9, 2004; 351(24): 2509 - 2518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Aarsland, C. G. Ballard, and G. Halliday Are Parkinson's Disease with dementia and Dementia with lewy Bodies the Same Entity? J Geriatr Psychiatry Neurol, September 1, 2004; 17(3): 137 - 145. [Abstract] [PDF]
|
|
|
|
|
|
D Aarsland, I Litvan, D Salmon, D Galasko, T Wentzel-Larsen, and J P Larsen Performance on the dementia rating scale in Parkinson's disease with dementia and dementia with Lewy bodies: comparison with progressive supranuclear palsy and Alzheimer's disease J. Neurol. Neurosurg. Psychiatry, September 1, 2003; 74(9): 1215 - 1220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Tiraboschi, L. A. Hansen, M. Alford, A. Merdes, E. Masliah, L. J. Thal, and J. Corey-Bloom Early and Widespread Cholinergic Losses Differentiate Dementia With Lewy Bodies From Alzheimer Disease Arch Gen Psychiatry, October 1, 2002; 59(10): 946 - 951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D Aarsland, K Laake, J P Larsen, and C Janvin Donepezil for cognitive impairment in Parkinson's disease: a randomised controlled study J. Neurol. Neurosurg. Psychiatry, June 1, 2002; 72(6): 708 - 712. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
